Candidate: A board certified pediatric cardiologist, in the Division of Pediatric Cardiology UCHSC, Denver, CO. MD from the University of South Florida, Tampa, FL., and trained in Pediatrics at the University of Cincinnati, Children's Hospital. Further clinical sub-specialty training in Pediatric Cardiac Transplantation with Dr. Mark Boucek at the Children's Hospital, Denver, CO. A Bugher Physician Scientist, and Instructor, focusing on clinical cardiac transplantation since 1994. His research interest has been immune mechanism in cardiac disease. He has established a heterotopic C.B-17 scid mouse model, which will be used in the outlined program. He now seeks to apply this clinical and research background to initiate research in cardiac allograft transplantation, benefit from the guidance of the Sponsor and his program to develop into an independent investigator. Research: The immune mechanism(s) and cell phenotypes responsible for cardiac allograft rejection remain unclear. The applicant proposes adoptive transfer of lymphoid cells into a C.B-17 scid mice transplanted with a heterotopic cardiac allograft to study cellular mechanism(s) of allograft rejection. Previous studies and preliminary data suggest that cardiac allograft rejection is CD4+ T cell dependent. He will test the general hypothesis: CD4+ T cells alone are not sufficient to reject cardiac allograft. He postulates that Lymphoid subpopulations (CD4+, CD8+ T cells, B cells, and NK cells) are components of either the afferent or efferent limbs of the response. The goals are to (1) determine the phenotype(s) of lymphoid cells in the afferent limb required to initiate cardiac allograft rejection, (2) the phenotypes in the efferent mechanism(s), and (3) the requirements for donor vs host MHC restriction required to recognize, initiate and attack the allograft. Environment: Clinical transplantation and transplantation research is a major emphasis of the UCHSC, the study of allograft rejection, tolerance and xenografting is the focus of Dr. Gill's lab, (the sponsor). The laboratory environment at UCHSC comprises excellent clinicians/scientists with backgrounds in transplantation, immunology, and molecular biology, state of the art equipment, technical, computer, statistics, and experimental design support, and a record of supporting and preparing Junior faculty for successful careers as independent investigators. Educational and research seminars of the UCHSC, National Jewish Center for Immunology, and the clinical eminence of the regional Pediatric Cardiac Transplant Program at the Children's Hospital enhance the environment for career development.